Aggregometers detect platelet aggregation in whole blood by passing a very small electric current between two electrodes immersed in a sample of blood or PRP (platelet rich plasma) and measuring the electrical impedance between the electrodes. During initial contact with the blood or PRP, the electrodes become coated with a monolayer of platelets. When an aggregating agent is added, platelets gradually accumulate on the monolayer coating, increasing the impedance between the electrodes. The change in impedance is recorded as a function of time on a strip chart recorder.
It is important to distinguish between platelet aggregation and clotting because the electrode structure devices which have in the past been developed for measuring clotting times are not operative for detecting and measuring platelet aggregation. Aggregation and clotting are two distinctly different hematological phenomena, and the differences are described in Chapter 1 of "Hemorrhage and Thrombosis" by Drs. Salzmann and Britten. In essence, platelet aggregation occurs during primary hemostasis, while clotting occurs during secondary hemostasis. It is stated that platelet aggregation in response to pharmacologically active substances such as ADP is largely independent of blood coagulation or clotting. The essential part of coagulation is the conversion of a soluble protein, fibrinogen, into an insoluble network of fibers, fibrin. In a time sense, the process of platelet aggregation is complete before coagulation or clotting has occurred. Typical of devices for measuring clotting times are the Rosenthal, U.S. Pat. No. 2,555,937, and to Stoner U.S. Pat. No. 3,840,806. These devices will not measure platelet aggregation.
A suitable electrode structure for the purpose of measuring platelet aggregation has been developed by Cardinal and Flower and is disclosed in U.S. Pat. No. 4,319,194. This patent covers specifically an electrode for measuring platelet aggregation in whole blood or PRP, using a wire electrode, and has eliminated the need for centrifuging blood to obtain PRP and PPP (platelet poor plasma.) and then using these plasmas to measure aggregation of platelets optically. The ability to speed up the tests, reduce labor costs, and test the platelets in their natural milieu was an important advance in platelet studies. The measurement in whole blood also allows studies to be performed in cases where optical aggregation does not work, such as with giant platelets (Bernard-Soulier syndrome), where red cells have been lysed or where it is impossible to obtain enough blood to make PRP and PPP, such as with small animals or babies. However, the use of a wire electrode as taught in the Cardinal and Flower patent has disadvantages. As a first matter, although precious metal electrodes are superior to base metals since base metals drift in blood/saline mixtures, precious metal electrodes are expensive. Moreover, any electrode made with wires requires expensive handling of individual electrode assemblies and parts during fabrication, whether the electrodes are made by insertion molding, hand fabrication or machine fabrication.
Accordingly, there is a need for a disposable platelet aggregation measuring system in which the items in contact with the sample, such as the cuvette. the electrode and the stirring agitator, are thrown away after a single use, particularly in clinical applications. This need is due to the fact that the doctor or medical technician doing the test is handling blood or plasma from patients or animals and is therefore exposed to diseases transmitted through these fluids. With a "single use" disposable system, it is not necessary to retrieve, cleanse and re-use the electrode assembly and/or other items such as the stir bar that have been in contact with the blood.
This problem has always existed, as for example with regard to hepatitis which has long been recognized as a danger to the doctor or technician. More recently the problem has been severely exacerbated by the presently accepted theory that AIDS is transmitted via body fluids. At present, AIDS is a fatal, incurable and non-preventable disease. Therefore, there is even greater reluctance on the part of the medical profession to handle blood where not necessary.